University of California

Other

J Jay Gargus

K George Chandy

George A Gutman

Katarin Kalman

Emmanuelle Fantino

Hiroaki Tomita

Vikram Shakkottai

Mark Estacion

The present invention is based on the discovery and cloning of the human small conductance calcium activated potassium channel type 3 (hKCa3/KCNN3) gene, which is expressed in neuronal cells, skeletal muscle, heart, and lymphocytes. Alterations in the hKCa3/KCNN3 gene or its protein product may enhance susceptibility to schizophrenia and/or bipolar disorder. hKCa3/KCNN3 may be involved in neuropsychiatric, neurological, neuromuscular, and immunological disorders. Substantially purified hKCa3/KCNN3 polypeptides and polynucleotides are provided. Antibodies which bind to hKCa3/KCNN3 polypeptides are also disclosed. A method for identifying a compound which affects hKCa3/KCNN3 polynucleotide or polypeptide is provided. A method for diagnosis and determining the prognosis and treatment regimen of a subject having or at risk of having a hKCa3/KCNN3-associated disorder is also provided. A method of treating a subject having or at risk of having an hKCa3/KCNN3-associated disorder by administering a therapeutically effective amount of a polynucleotide encoding SEQ ID NO:2 is also provided. A formulation for administration of hKCa3/KCNN3 to a patient of a therapeutically effective amount of hKCa3/KCNN3 polypeptide is provided. Kits useful for detecting the presence of hKCa3/KCNN3 polypeptide or polynucleotide in a sample from a subject having a hKCa3/KCNN3-associated disorder are provided. Transgenic nonhuman animals having a transgene encoding hKCa3/KCNN3 are also described.

hKCa3/KCNN3 small conductance calcium activated potassium channel: a diagnostic marker and therapeutic target

The present invention is based on the discovery and cloning of two variants of the small conductance calcium activated potassium channel type 3 (hKCa3/KCNN3) gene. The isoform variants are identical to the structure of the SKCa3-1a transcript with regard to exons 2&#x2013;8, but differ in that one variant, SKCa3-1b, contains exon 1b in place of exon 1a and in that the other variant, SKCa3-1c, contains exon 1c in place of exon 1a. When expressed simultaneously with SKCa3-1a, the variants will independently dominantly negatively suppress SKCa3-1a and other functional members of the SKchannel family. Accordingly, the present invention provides the novel gene variants, methods for the detection of the variants and treatment of disorders related to the activity of these variants. Kits employing the methods of the invention are also described.

Exons of the hSKCa3/KCNN3 gene

hKCa3/KCNN3 small conductance calcium activated potassium channel: A diagnostic marker and therapeutic target

A method for diagnosing a congenital disease by determining a cell's response to activation of a membrane receptor using a physiological indicator is provided. The method of the invention uses fetal or adult cells in a non-invasive screen for congenital disorders.

Method of detection of congenital disease

The present invention is based on the discovery and cloning of the human small conductance calcium activated potassium channel type 3 (hKCa3/KCNN3) gene, which is expressed in neuronal cells, skeletal muscle, heart, and lymphocytes. Alterations in the hKCa3/KCNN3 gene or its protein product may enhance susceptibility to schizophrenia and/or bipolar disorder. hKCa3/KCNN3 may be involved in neuropsychiatric, neurological, neuromuscular, and immunological disorders. Substantially purified hKCa3/KNN3 polypeptides and polynucleotides are provided. Antibodies which bind to hKCa3/KCNN3 polypeptides are also disclosed. A method for identifying a compound which affects hKCa3/KCNN3 polynucleotide or polypeptide is provided. A method for diagnosis and determining the prognosis and treatment regimen of a subject having or at risk of having a hKCa3/KCNN3-associated disorder is also provided. A method of treating a subject having or at risk of having an hKCa3/KCNN3-associated disorder by administering a therapeutically effective amount of a polynucleotide encoding SEQ ID NO:2 is also provided. A formulation for administration of hKCa3/KCNN3 to a patient of a therapeutically effective amount of hKCa3/KCNN3 polypeptide is provided. Kits useful for detecting the presence of hKCa3/KCNN3 polypeptide or polynucleotide in a sample from a subject having a hKCa3/KCNN3-associated disorder are provided. Transgenic nonhuman animals having a transgene encoding hKCa3/KCNN3 are also described.

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Irvine, CA, United States of America

J Jay Gargus